tbuckley/cabot-search huggingface dataset:
Endoscopic intermuscular dissection for deep submucosal invasive cancer in the rectum. Is this the dawn of the endoscopic cancer surgeon?
Authors: Gaius Longcroft-Wheaton
Journal: Endoscopy (2022)

Over the last 15 years, the paradigm concerning treatment of colorectal neoplasia has shifted massively, with a progressive move away from conventional surgery towards less invasive endoscopic techniques. What was once a feared and controversial approach is now standard of care and, for benign pathology, endoscopic resection has become accepted as the best approach, even for very large and challenging lesions, with surgery being restricted to cases where endoscopic approaches have failed. The techniques used have also progressed, from piecemeal endoscopic mucosal resection (EMR) towards en bloc resection using a submucosal dissection technique (e. g. endoscopic submucosal dissection [ESD]). This has enabled the endoscopist to be confident in the completeness of the resection, with R0 resections becoming possible. With this shift has come a challenge around whether more invasive early cancers can also be managed in a similar manner.
Indoor microbiome, microbial and plant metabolites, chemical compounds, and asthma symptoms in junior high school students: a multicentre association study in Malaysia
Authors: Yu Sun, Mei Zhang, Zheyuan Ou, Yi Meng, Yang Chen, Ruqin Lin, Jamal Hisham Hashim, Zailina Hashim, Gunilla Wieslander, Qingsong Chen, Dan Norbäck, Xi Fu
Journal: European Respiratory Journal (2022)

Indoor microbial exposure is associated with asthma, but the health effects of indoor metabolites and chemicals have not been comprehensively assessed.We collected classroom dust from 24 junior high schools in three geographically distanced areas in Malaysia (Johor Bahru, Terengganu and Penang), and conducted culture-independent high-throughput microbiome and untargeted metabolomics/chemical profiling.1290 students were surveyed for asthma symptoms (wheeze). In each centre, we found significant variation in the prevalence of wheeze among schools, which could be explained by personal characteristics and air pollutants. Large-scale microbial variations were observed between the three centres; the potential protective bacteria were mainly from phyla Actinobacteria in Johor Bahru, Cyanobacteria in Terengganu and Proteobacteria in Penang. In total, 2633 metabolites and chemicals were characterised. Many metabolites were enriched in low-wheeze schools, including plant secondary metabolites flavonoids/isoflavonoids (isoliquiritigenin, formononetin, astragalin), indole and derivatives (indole, serotonin, 1H-indole-3-carboxaldehyde), and others (biotin, chavicol). A neural network analysis showed that the indole derivatives were co-occurring with the potential protective microbial taxa, including Actinomycetospora, Fischerella and Truepera, suggesting these microorganisms may pose health effects by releasing indole metabolites. A few synthetic chemicals were enriched in high-wheeze schools, including pesticides (2(3H)-benzothiazolethione), fragrances (2-aminobenzoic acid, isovaleric acid), detergents and plastics (phthalic acid), and industrial materials (4,4-sulfonyldiphenol).This is the first association study between high-throughput indoor chemical profiling and asthma symptoms. The consistent results from the three centres indicate that indoor metabolites/chemicals could be a better indicator than the indoor microbiome for environmental and health assessments, providing new insights for asthma prediction, prevention and control.
Endoscopy International Open – recently published
Journal: Endoscopy (2022)

Comment on: Resection depth for small colorectal polyps comparing cold snare polypectomy, hot snare polypectomy and underwater endoscopic mucosal resectionEndosc Int Open 2022; 10(05): E602-E608DOI: 10.1055/a-1785-8616 Comment on: Efficacy of specimen pasting after cold snare polypectomy for pathological evaluation of horizontal marginsEndosc Int Open 2022; 10(05): E572-E579DOI: 10.1055/a-1784-6723 Comment on: Effectiveness and safety of endoscopic submucosal dissection using the pocket creation method in the Japanese population: a systematic review and meta-analysisEndosc Int Open 2022; 10(05): E694-E702DOI: 10.1055/a-1789-0548
Real-world trends in incidence of bacterial sexually transmissible infections among gay and bisexual men using HIV pre-exposure prophylaxis (PrEP) in Australia following nationwide PrEP implementation: an analysis of sentinel surveillance data
Authors: Michael W Traeger, Rebecca Guy, Jason Asselin, Prital Patel, Allison Carter, Edwina J Wright, Andrew Grulich, Hamish McManus, Christopher K Fairley, Eric P F Chow, Anna McNulty, Robert Finlayson, Charlotte Bell, Louise Owen, Lewis Marshall, Darren Russell, Darryl O'Donnell, Basil Donovan, Margaret E Hellard, Mark A Stoové, Jason Asselin, Lisa Bastian, Deborah Bateson, Scott Bowden, Mark Boyd, Denton Callander, Allison Carter, Aaron Cogle, Jane Costello, Wayne Dimech, Jennifer Dittmer, Basil Donovan, Carol El-Hayek, Jeanne Ellard, Christopher Fairley, Lucinda Franklin, Rebecca Guy, Margaret Hellard, Jane Hocking, Jules Kim, Scott McGill, David Nolan, Prital Patel, Stella Pendle, Victoria Polkinghorne, Long Nguyen, Thi Nguyen, Catherine O'Connor, Philip Reed, Norman Roth, Nathan Ryder, Christine Selvey, Mark Stoové, Michael William Traeger, Toby Vickers, Melanie Walker, Lucy Watchirs-Smith, Michael West
Journal: The Lancet Infectious Diseases (2022)
Serum extracellular vesicles for delivery of CRISPR-CAS9 ribonucleoproteins to modify the dystrophin gene
Authors: Nathalie Majeau, Annabelle Fortin-Archambault, Catherine Gérard, Joël Rousseau, Pouiré Yaméogo, Jacques P. Tremblay
Journal: Molecular Therapy (2022)

Extracellular vesicles (EVs) mediate intercellular biomolecule exchanges in the body, making them promising delivery vehicles for therapeutic cargo. Genetic engineering by the CRISPR system is an interesting therapeutic avenue for genetic diseases such as Duchenne muscular dystrophy (DMD). We developed a simple method for loading EVs with CRISPR ribonucleoproteins (RNPs) consisting of SpCas9 proteins and guide RNAs (gRNAs). EVs were first purified from human or mouse serum using ultrafiltration and size-exclusion chromatography. Using protein transfectant to load RNPs into serum EVs, we showed that EVs are good carriers of RNPs in vitro and restored the expression of the tdTomato fluorescent protein in muscle fibers of Ai9 mice. EVs carrying RNPs targeting introns 22 and 24 of the DMD gene were also injected into muscles of mdx mice having a non-sense mutation in exon 23. Up to 19% of the cDNA extracted from treated mdx mice had the intended deletion of exons 23 and 24, allowing dystrophin expression in muscle fibers. RNPs alone, without EVs, were inefficient in generating detectable deletions in mouse muscles. This method opens new opportunities for rapid and safe delivery of CRISPR components to treat DMD.
Mechanism of effective combination radio-immunotherapy against 9464D-GD2, an immunologically cold murine neuroblastoma
Authors: Taylor J Aiken, Amy K Erbe, Lauren Zebertavage, David Komjathy, Arika S Feils, Matthew Rodriguez, Ashley Stuckwisch, Stephen D Gillies, Zachary S Morris, Jen Birstler, Alexander L Rakhmilevich, Paul M Sondel
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Most pediatric cancers are considered immunologically cold with relatively few responding to immune checkpoint inhibition. We recently described an effective combination radio-immunotherapy treatment regimen ( c ombination a daptive- i nnate immunotherapy r egimen (CAIR)) targeting adaptive and innate immunity in 9464D-GD2, an immunologically cold model of neuroblastoma. Here, we characterize the mechanism of CAIR and the role of major histocompatibility complex class I (MHC-I) in the treatment response. Methods Mice bearing GD2-expressing 9464D-GD2 tumors were treated with CAIR (external beam radiotherapy, hu14.18-IL2 immunocytokine, CpG, anti-CD40, and anti-CTLA4) and tumor growth and survival were tracked. Depletion of specific immune cell lineages, as well as testing in immunodeficient R2G2 mice, were used to determine the populations necessary for treatment efficacy. Induction of MHC-I expression in 9464D-GD2 cells in response to interferon-γ (IFN-γ) and CAIR was measured in vitro and in vivo , respectively, by flow cytometry and quantitative real-time PCR. A cell line with IFN-γ-inducible MHC-I expression (9464D-GD2-I) was generated by transfecting a subclone of the parental cell line capable of expressing MHC-I with GD2 synthase and was used in vivo to assess the impact of MHC-I expression on responsiveness to CAIR. Results CAIR cures some mice bearing small (50 mm 3 ) but not larger (100 mm 3 ) 9464D-GD2 tumors and these cured mice develop weak memory responses against tumor rechallenge. Early suppression of 9464D-GD2 tumors by CAIR does not require T or natural killer (NK) cells, but eventual tumor cures are NK cell dependent. Unlike the parental 9464D cell line, 9464D-GD2 cells have uniformly very low MHC-I expression at baseline and fail to upregulate expression in response to IFN-γ. In contrast, 9464D-GD2-I upregulates MHC-I in response to IFN-γ and is less responsive to CAIR. Conclusion Treatment with CAIR cures 9464D-GD2 tumors in a NK cell dependent manner and induction of MHC-I by tumors cells was associated with decreased efficacy. These results demonstrate that the early tumor response to this regimen is T and NK cell independent, but that NK cells have a role in generating lasting cures in the absence of MHC-I expression by tumor cells. Further strategies to better inhibit tumor outgrowth in this setting may require further NK activation or the ability to engage alternative immune effector cells.
Treosulfan compared with <scp>reduced‐intensity</scp> busulfan improves allogeneic hematopoietic cell transplantation outcomes of older acute myeloid leukemia and myelodysplastic syndrome patients: Final analysis of a prospective randomized trial
Authors: Dietrich W. Beelen, Matthias Stelljes, Péter Reményi, Eva‐Maria Wagner‐Drouet, Peter Dreger, Wolfgang Bethge, Fabio Ciceri, Friedrich Stölzel, Christian Junghanß, Hélène Labussiere‐Wallet, Kerstin Schaefer‐Eckart, Goetz U. Grigoleit, Christof Scheid, Francesca Patriarca, Alessandro Rambaldi, Dietger Niederwieser, Inken Hilgendorf, Domenico Russo, Gérard Socié, Ernst Holler, Bertram Glass, Jochen Casper, Gerald Wulf, Nadezda Basara, Maria Bieniaszewska, Gernot Stuhler, Mareike Verbeek, Ursula La Rocca, Jürgen Finke, Fabio Benedetti, Uwe Pichlmeier, Anja Klein, Joachim Baumgart, Miroslaw Markiewicz
Journal: American Journal of Hematology (2022)

Abstract The phase III study was designed to compare event‐free survival (EFS) after treosulfan‐based conditioning with a widely applied reduced‐intensity conditioning (RIC) busulfan regimen in older or comorbid patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT). A previously reported confirmatory interim analysis of the randomized clinical study including 476 patients demonstrated statistically significant noninferiority for treosulfan with clinically meaningful improvement in EFS. Here, the final study results and pre‐specified subgroup analyses of all 570 randomized patients with completed longer‐term follow‐up are presented. Patients presenting HCT‐specific comorbidity index &gt;2 or aged ≥50 years were randomly assigned (1:1) to intravenous (IV) fludarabine with either treosulfan (30 g/m 2 IV) or busulfan (6.4 mg/kg IV) after stratification by disease risk group, donor type, and participating institution. The primary endpoint was EFS with disease recurrence, graft failure, or death from any cause as events. EFS of patients (median age 60 years) was superior after treosulfan compared to RIC busulfan: 36‐months‐EFS rate 59.5% (95% CI, 52.2–66.1) vs. 49.7% (95% CI, 43.3–55.7) with a hazard ratio (HR) of 0.64 (95% CI, 0.49–0.84), p = 0.0006. Likewise, overall survival (OS) with treosulfan was superior compared to busulfan: 36‐month‐OS rate 66.8% vs. 56.3%; HR 0.64 (95% CI, 0.48–0.87), p = 0.0037. Post hoc analyses revealed that these differences were consistent with the confirmatory interim analysis, and thereby the treosulfan regimen appears particularly suitable for older AML and MDS patients.
AZD5305 More Tolerable than Earlier PARP Agents
Journal: Cancer Discovery (2022)

Findings from the phase I/IIa trial of AZD5305, a next-generation, highly selective PARP1 inhibitor, indicate that the drug is better tolerated in patients with ovarian, HER2-negative breast, pancreatic, and prostate cancers with BRCA1/2, PALB2, and RAD51C mutations compared with first-generation PARP inhibitors. In addition, 25% of 40 evaluable patients had a partial response.
Understanding Prognosis: Discrepancy in Prognosis Estimates Between Patients With Cirrhosis and their Hepatologists
Authors: Alyson Kaplan, Lauren Comisar, Nneka N Ufere, Deanna Jannat-Khah, Russell Rosenblatt, Brett Fortune, Holly G Prigerson, Robert Brown
Journal: Clinical Gastroenterology and Hepatology (2022)
A novel endoscopic clip for closing a large perforating wound in a patient undergoing endoscopic full-thickness resection
Authors: Qiang Zhang, Zhen Wang
Journal: Endoscopy (2022)

The through-the-scope twin clip (Micro-Tech Co. Ltd., Nanjing, China), also called a dual action tissue clip, was first reported by us [1] [2]. The clip can pass directly through the working channel of the endoscope to close the wound and is convenient and quick to use. To our knowledge, this was the first time that through-the-scope twin clips were used to close a large perforation in a patient with a submucosal tumor.
Protection and Waning of Natural and Hybrid Immunity to SARS-CoV-2
Authors: Yair Goldberg, Micha Mandel, Yinon M. Bar-On, Omri Bodenheimer, Laurence S. Freedman, Nachman Ash, Sharon Alroy-Preis, Amit Huppert, Ron Milo
Journal: New England Journal of Medicine (2022)

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides natural immunity against reinfection. Recent studies have shown waning of the immunity provided by the BNT162b2 vaccine. The time course of natural and hybrid immunity is unknown.Using the Israeli Ministry of Health database, we extracted data for August and September 2021, when the B.1.617.2 (delta) variant was predominant, on all persons who had been previously infected with SARS-CoV-2 or who had received coronavirus 2019 vaccine. We used Poisson regression with adjustment for confounding factors to compare the rates of infection as a function of time since the last immunity-conferring event.The number of cases of SARS-CoV-2 infection per 100,000 person-days at risk (adjusted rate) increased with the time that had elapsed since vaccination with BNT162b2 or since previous infection. Among unvaccinated persons who had recovered from infection, this rate increased from 10.5 among those who had been infected 4 to less than 6 months previously to 30.2 among those who had been infected 1 year or more previously. Among persons who had received a single dose of vaccine after previous infection, the adjusted rate was low (3.7) among those who had been vaccinated less than 2 months previously but increased to 11.6 among those who had been vaccinated at least 6 months previously. Among previously uninfected persons who had received two doses of vaccine, the adjusted rate increased from 21.1 among those who had been vaccinated less than 2 months previously to 88.9 among those who had been vaccinated at least 6 months previously.Among persons who had been previously infected with SARS-CoV-2 (regardless of whether they had received any dose of vaccine or whether they had received one dose before or after infection), protection against reinfection decreased as the time increased since the last immunity-conferring event; however, this protection was higher than that conferred after the same time had elapsed since receipt of a second dose of vaccine among previously uninfected persons. A single dose of vaccine after infection reinforced protection against reinfection.
Prone Whole-Breast Radiotherapy—Better Than Supine?
Authors: Dean A. Shumway, Katelyn M. Atkins
Journal: JAMA Oncology (2022)

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Targeted alleviation of ischemic stroke reperfusion via atorvastatin-ferritin Gd-layered double hydroxide
Authors: Li Wang, Baorui Zhang, Xueting Yang, Shuaitian Guo, Geoffrey I.N. Waterhouse, Guangrong Song, Shanyue Guan, Aihua Liu, Liang Cheng, Shuyun Zhou
Journal: Bioactive Materials (2022)

In acute ischemic stroke therapy, potent neuroprotective agents are needed that prevent neural injuries caused by reactive oxygen species (ROS) during ischemic reperfusion. Herein, a novel 2D neuroprotective agent (AFGd-LDH) is reported, comprising Gd-containing layered double hydroxide nanosheets (Gd-LDH, as a drug nanocarrier/MRI contrast agent), atorvastatin (ATO, as a neuroprotective drug) and the ferritin heavy subunit (FTH, as a blood brain barrier transport agent). Experiments revealed AFGd-LDH to possess outstanding antioxidant activity, neuroprotective properties, blood‒brain barrier transit properties, and biocompatibility. In vitro studies demonstrated the ROS scavenging efficiency of AFGd‒LDH to be ∼90%, surpassing CeO2 (50%, a ROS scavenger) and edaravone (52%, a clinical neuroprotective drug). Ischemia‒reperfusion model studies in mice showed AFGd‒LDH could dramatically decrease apoptosis induced by reperfusion, reducing the infarct area by 67% and lowering the neurological deficit score from 3.2 to 0.9. AFGd-LDH also offered outstanding MRI performance, thus enabling simultaneous imaging and ischemia reperfusion therapy.
Commentary
Authors: Jan Martinek
Journal: Endoscopy (2022)

This case describes the unusual adverse event of delayed bleeding and intratunnel hematoma, occurring few hours after peroral endoscopic myotomy (POEM) carried out for esophageal achalasia. The authors reopened the mucosal incision and removed clots from the tunnel using a special grasper and a snare. They then stopped active bleeding with a coagrasper and finally applied hemostatic gel. The report shows that severe adverse events may occur after POEM and all endoscopists performing submucosal procedures should be aware of them. We can draw several teaching points from this interesting case. First, if endoscopic suturing had been used instead of clips, tunnel re-entry would have been more difficult: thus, the use of clips may be considered beneficial in this regard. Second, I do not think that computed tomography (CT) is always necessary in patients with clinical signs of bleeding after POEM. Third, I found the use of hemostatic gel interesting; ideally, the authors would have added a comment on whether its use outside the lumen might carry an additional risk of adverse events. A nice case, and congratulations to the authors on its successful outcome.
Gli1 promotes epithelial–mesenchymal transition and metastasis of non-small cell lung carcinoma by regulating snail transcriptional activity and stability
Authors: Xueping Lei, Zhan Li, Yihang Zhong, Songpei Li, Jiacong Chen, Yuanyu Ke, Sha Lv, Lijuan Huang, Qianrong Pan, Lixin Zhao, Xiangyu Yang, Zisheng Chen, Qiudi Deng, Xiyong Yu
Journal: Acta Pharmaceutica Sinica B (2022)

Metastasis is crucial for the mortality of non-small cell lung carcinoma (NSCLC) patients. The epithelial-mesenchymal transition (EMT) plays a critical role in regulating tumor metastasis. Glioma-associated oncogene 1 (Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein, we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.
Bempegaldesleukin plus Nivolumab in First-line Metastatic Urothelial Carcinoma: Results from PIVOT-02
Authors: Arlene O. Siefker-Radtke, Daniel C. Cho, Adi Diab, Mario Sznol, Mehmet A. Bilen, Arjun V. Balar, Giovanni Grignani, Erika Puente, Lily Tang, David Chien, Ute Hoch, Arkopal Choudhury, Danni Yu, Sue L. Currie, Mary A. Tagliaferri, Jonathan Zalevsky, Michael E. Hurwitz, Nizar M. Tannir
Journal: European Urology (2022)
A commentary on “Ultrasound-guided versus laparoscopic-guided subcostal transversus abdominis plane (TAP) block versus No TAP block in laparoscopic cholecystectomy; a randomized double-blind controlled trial” (Int. J. Surg. 2022;101:106639)
Authors: Xin-Tao Li, Fu-Shan Xue, Tian Tian
Journal: International Journal of Surgery (2022)